PNH develops when a genetic mutation leads to the production of defective red blood cells. This mutation typically occurs in adults and is not inherited from your parents or passed on to your children.
The PNH disease process starts in your bone marrow, which produces cells known as hematopoietic stem cells. These cells eventually grow and mature into red blood cells, white blood cells, and platelets. In PNH, a mutation occurs in one of these stem cells, in what’s known as the PIGA gene. This abnormal stem cell then divides over and over to produce many abnormal stem cells, which go on to become abnormal red blood cells.
Many experts believe that the mutation that causes PNH also happens in healthy people, and only leads to disease — with abnormal stem cells multiplying quickly — when people have underlying bone marrow dysfunction. Weakened bone marrow may occur due to aplastic anemia or another bone marrow disease, which may be mild or undiagnosed, according to the Aplastic Anemia and MDS International Foundation (AAMDSIF).
The abnormal red blood cells that develop in PNH — known as PNH red blood cells to differentiate them from your healthy red blood cells — lack a protective shield of proteins. Without this shield, they are vulnerable to attack and destruction by a part of your immune system known as the complement system.
When PNH red blood cells are attacked by your complement system, they break apart and release hemoglobin — a protein that carries oxygen throughout your body — into your blood. When this red blood cell destruction (hemolysis) happens faster than new red blood cells can be produced, it leads to anemia (inadequate red blood cells).
When there is too much hemoglobin in your blood — known as free hemoglobin when it’s not in red blood cells — your body may try to “clean up” this hemoglobin by releasing a substance known as nitric oxide, depleting your body’s supply of nitric oxide in the process. This depletion can lead to sudden muscle or esophageal spasms.
Abnormal stem cells in PNH may also develop into abnormal platelets, which can lead to dangerous blood clots in different areas of the body. It’s also possible that red blood cell destruction may contribute to an increased clotting risk.
You’re more likely to develop PNH if:
- You’re between 30 and 40 years old
- You have aplastic anemia or another bone marrow disorder
More than 1 in 10 people with aplastic anemia will develop PNH, according to AAMDSIF. Some people with PNH may also go on to develop aplastic anemia.
